Calcium is an essential structural component of both teeth and bones. Furthermore, the calcium cation plays a key role in numerous fundamental biological processes. Calcium metabolism in the vertebrates is controlled largely by three hormones: parathyroid hormone (PTH), thyrocalcitonin, cholecalciferol. The current proposal is designed to further the elucidation of the biological action of parathyroid hormone at a molecular level. Tryptophan and histidine residues of native bovine parathyroid hormone (PTH) and the corresponding synthetic, biologically active 1-34 amino acid sequence will be modified chemically. Biological activity and immunonological reactivity of the resulting derivatives will be compared with the original material in order to elucidate the specific biological roles of the appropriate amino acid residues. In assessing the data, consideration will be given to the potential role of conformational changes which may result from the labelling of the residues in question.